InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Cbl

Summary

InnateDB Protein

IDBP-155972.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

Cbl

Protein Name

Casitas B-lineage lymphoma

Synonyms

4732447J05Rik; c-Cbl; cbl; Cbl-2;

Species

Mus musculus

Ensembl Protein

ENSMUSP00000041902

InnateDB Gene

IDBG-155970 (Cbl)

Protein Structure

UniProt Annotation

Function

Adapter protein that functions as a negative regulator of many signaling pathways that are triggered by activation of cell surface receptors. Acts as an E3 ubiquitin-protein ligase, which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, and then transfers it to substrates promoting their degradation by the proteasome. Recognizes activated receptor tyrosine kinases, including KIT, FLT1, FGFR1, FGFR2, PDGFRA, PDGFRB, EGFR, CSF1R, EPHA8 and KDR and terminates signaling. Recognizes membrane-bound HCK, SRC and other kinases of the SRC family and mediates their ubiquitination and degradation. Participates in signal transduction in hematopoietic cells. Plays an important role in the regulation of osteoblast differentiation and apoptosis. Essential for osteoclastic bone resorption. The 'Tyr-737' phosphorylated form induces the activation and recruitment of phosphatidylinositol 3-kinase to the cell membrane in a signaling pathway that is critical for osteoclast function. May be functionally coupled with the E2 ubiquitin-protein ligase UB2D3. {ECO:0000269PubMed:10393178, ECO:0000269PubMed:12649282, ECO:0000269PubMed:19265199, ECO:0000269PubMed:20100865, ECO:0000269PubMed:9653117}.

Subcellular Localization

Cytoplasm. Cell membrane {ECO:0000250}. Note=Colocalizes with FGFR2 in lipid rafts at the cell membrane. {ECO:0000250}.

Disease Associations

Note=Can be converted to an oncogenic protein by deletions or mutations that disturb its ability to down-regulate RTKs.

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 78 experimentally validated interaction(s) in this database.
They are also associated with 203 interaction(s) predicted by orthology.

Experimentally validated
Total	78 [view]
Protein-Protein	77 [view]
Protein-DNA	1 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	203 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0001784	phosphotyrosine binding
GO:0004842	ubiquitin-protein transferase activity
GO:0004871	signal transducer activity
GO:0005509	calcium ion binding
GO:0005515	protein binding
GO:0008270	zinc ion binding
GO:0016874	ligase activity
GO:0017124	SH3 domain binding
GO:0046872	metal ion binding
GO:0046875	ephrin receptor binding

Biological Process

GO:0006468	protein phosphorylation
GO:0007166	cell surface receptor signaling pathway
GO:0014068	positive regulation of phosphatidylinositol 3-kinase signaling
GO:0016567	protein ubiquitination
GO:0043066	negative regulation of apoptotic process
GO:0045087	innate immune response (InnateDB)
GO:0045453	bone resorption

Cellular Component

GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0005886	plasma membrane
GO:0016600	flotillin complex

Protein Structure and Domains

PDB ID

MGI:88279

InterPro

IPR000449 Ubiquitin-associated domain/translation elongation factor EF-Ts, N-terminal
IPR000980 SH2 domain
IPR001841 Zinc finger, RING-type
IPR003153 Adaptor protein Cbl, N-terminal helical
IPR009060 UBA-like
IPR014741 Adaptor protein Cbl, EF hand-like
IPR014742 Adaptor protein Cbl, SH2-like
IPR015940 Ubiquitin-associated/translation elongation factor EF1B, N-terminal, eukaryote
IPR018957 Zinc finger, C3HC4 RING-type

PFAM